Some polymers are known to degrade by hydrolysis in the presence of water and thereby decompose to smaller chemical units. Some of these polymers are also biodegradable, such as polylactic acid and polyglycolic acid. Due to the expense and difficulty in preparing these hydrolytically degradable polymers, their use has been largely confined to high value medical applications where bioabsorbable materials are required. Most reported medical applications involve internal use of the polymers, such as for sutures, prosthetic devices, and drug release matrices. Some polymers that have received considerable attention for medical applications include polylactic acid, polyglycolic acid, poly-.epsilon.-caprolactone and polydioxanone.
Medical applications, however, involve relatively predictable and constant environmental conditions to which the polymers are subjected during use, i.e., the human body. Therefore, the need to manipulate or modify the properties of polymers used in such medical applications has not been great.
Some attempts, however, have been made in the medical field to vary properties of bioabsorbable polymers based on the specific intended use. Properties that have received some attention include strength, flexibility, and rate of hydrolytic degradation. It is generally known that a copolymer usually exhibits different properties than homopolymers of either individual comonomer. Some attempts have been made to develop specific copolymers for specific medical applications.
For example, various copolymers containing lactic acid repeating units and glycolic acid repeating units have been suggested for various uses. For example, U.S. Pat. No. 3,867,190 by Schmitt et al., issued Feb. 18, 1975, discusses medical uses for a copolymer containing, by mole percent, from about 15 to 85% glycolic acid and from about 85 to 15% lactic acid. U.K. Patent Application Publication No. 2223027A by Ikada et al., published Mar. 28, 1990, discusses the use of lactide/glycolide copolymers for regenerative treatment of the periodontium.
Medical uses for copolymers containing .epsilon.-caprolactone and lactide have also been suggested. U.K. Patent Application Publication No. 2223027A also discusses the use of a lactide/.epsilon.-caprolactone copolymer, also for regenerative treatment of the periodontium. U.S. Pat. No. 4,643,734 by Lin, issued Feb. 17, 1987, discusses composite surgical articles made from carbon fibers and lactide/.epsilon.-caprolactone copolymers. Preferably, the copolymer contains from about 60 to about 95 weight percent .epsilon.-caprolactone. The resulting composite is reported to not be stiff.
U.S. Pat. No. 5,085,629 by Goldberg et al., issued Feb. 4, 1992, discusses a terpolymer of L-lactide, glycolide and .epsilon.-caprolactone for use as a biocompatible, biodegradable, resorbable infusion stent composed of from about 15 to about 25 weight percent .epsilon.-caprolactone, from about 45 to about 85 weight percent L-lactide, and from about 5 to about 50 weight percent glycolide. It is stated that the controlling factor in the stiffness of the terpolymer composition is the relative amount of .epsilon.-caprolactone monomer.
U.S. Pat. No. 4,643,191 by Bezwada et al., issued Feb. 17, 1987, discusses a crystalline copolymer produced by first polymerizing p-dioxanone to form a mixture of monomer and homopolymer, and then adding lactide to this mixture and polymerizing to form a copolymer. The polymers discussed are useful for the manufacture of surgical devices, and in particular, absorbable monofilament sutures and ligatures and hemostatic ligating clips. The polymers are reported to be more pliable than p-dioxanone homopolymers.
In addition to glycolide and .epsilon.-caprolactone, several other comonomers have been reported for possible polymerization with lactic acid or lactide. U.S. Pat. No. 3,636,956 by Schneider, issued Jan. 25, 1972, discusses absorbable sutures prepared by extrusion of a polylactide polymer, including copolymers containing up to about 15 percent by weight of specific comonomer repeating units. Specific examples show polymerization of L-lactide with each of 5% .beta.-propiolactone, 5% .beta.-butyrolactone, 5% pivalolactone, 11.6% intermolecular cyclic ester of .alpha.-hydroxybutyric acid, and 10% intermolecular cyclic ester of .alpha.-hydroxyheptanoic acid. U.S. Pat. No. 4,481,353 by Nyilas et al., issued Nov. 6, 1984, discusses bioresorbable polyesters that are useful in making surgical articles. The polyesters are composed of a Krebs Cycle dicarboxylic acid or isomer or anhydride thereof, a diol having 2, 4, 6, or 8 carbon atoms, and an alphahydroxycarboxylic acid, which can be glycolic acid, L-lactic acid, D-lactic acid, or racemic lactic acid. U.S. Pat. No. 5,066,772 by Tang et al., issued Nov. 19, 1991, discusses bioabsorbable copolymers containing carbonate repeating units and 2-hydroxycarboxylic acid repeating ester units useful for fabricating medical devices. It is reported that, by selection and placement of monomeric units in the polymeric chain, as well as other variables, various properties of the copolymer can be tailored for various medical applications.
Many references, however, list several possible comonomers without any consideration for the possible effects that such comonomers might have on properties of the copolymer. For example, U.S. Pat. No. 2,703,316 by Schneider, issued Mar. 1, 1955, discusses lactide polymers and copolymers with up to 50% of another polymerizable cyclic ester having a 6- to 8-membered ring, capable of being formed into a tough, orientable, self-supporting thin film. The patent specifically discloses polymerization of 5 parts lactide and 5 parts glycolide and also polymerization of 12 parts lactide and 2 parts tetramethylglycolide, but also provides an extensive list of other possible comonomers with no elaboration on polymer properties.
A few references have suggested the use of hydrolytically degradable polymers outside of the medical field. For example, U.S. Pat. No. 4,057,537 by Sinclair, issued Nov. 8, 1977, discusses copolymers of L-lactide and .epsilon.-caprolactone prepared from a mixture of comonomers containing from about 50 to about 97 weight percent L-lactide and the remainder .epsilon.-caprolactone. Strength and elasticity are shown to vary depending on the relative amounts of L-lactide and .epsilon.-caprolactone monomers. Depending upon the L-lactide/.epsilon.-caprolactone ratio, the polymers are disclosed to be useful for the manufacture of films, fibers, moldings, and laminates. However, no specific applications are discussed. Sinclair discloses that plasticizers may be added to the copolymer if desired, but provides no guidance concerning what compounds might be suitable.
Although it has been noted that suitable compounds, such as plasticizers, may be added to modify the properties of some hydrolytically degradable polymers, such as in U.S. Pat. No. 4,057,537 just discussed, little guidance has been given as to what compounds might be effective. Identifying suitable compounds for use in modifying the properties of biodegradable polymers has been a major problem confronted in developing biodegradable polymers for mass-marketed products. Relatively few references discuss modification of properties of hydrolytically degradable polymers with external compounds, such as polylactide homopolymers and copolymers. The medical industry has generally sought to tailor polymer compositions to specific medical applications by developing specific copolymers, rather than to add external compounds. Those references that do discuss compounds, such as plasticizers, however, offer little guidance in selecting suitable compounds to be used for mass-marketed, hydrolytically degradable polymer products.
Compounds which effectively modify properties of polymer products are not to be confused with compounds that are designed only to aid polymer processing and that are removed prior to or during manufacture of the final product. Compounds which are effective to modify properties of polymer products should be completely miscible with the polymer, nonvolatile, and should not migrate to the surface of the polymer composition, as might be desirable with a processing aid designed to increase lubrication, as noted.
The use of plasticizers or other compounds to modify properties in mass-marketed products, such as packaging films and containers, presents several problems that are not apparent with nondegradable polymers or with hydrolytically degradable polymers used in specialty markets, such as for medical applications. Plasticizers or other similar compounds used in mass-marketed products made of hydrolytically degradable polymers will be deposited into the environment in large quantities upon degradation of the polymers. Therefore even low levels of toxicity are a concern due to the potentially huge quantity of potential waste. Toxicity is not as big of a problem with nondegradable polymers because plasticizers remain largely locked inside the polymer composition. Toxicity is not a major problem with medical applications which result in relatively little environmental contamination because the market is so much smaller. Also, low toxicity plasticizers in medical applications are present in such small quantities and are released at such slow rates such that there is reduced potential for toxicological problems. The prior art is not informative, however, concerning the use of plasticizers with hydrolytically degradable polymers, and particularly with biodegradable polymers. As noted, medical industries have tended to attempt development of specific copolymers for different medical applications. Those references that do discuss plasticization of hydrolytically degradable polymers using external plasticizers offer little insight into the special problems, as noted, concerning plasticization of mass-marketed degradable polymer compositions. Because of the potential cost advantages over specifically designed copolymers alone and because of the wide flexibility offered by effective plasticizers, a great need exists for suitable plasticized hydrolytically degradable polymer compositions.
Many of the references discussing "plasticizing" additives for hydrolytically degradable polymers to soften the composition are, in effect, processing aids that are either not present in the final product, or if present, are not incorporated into the product to provide effective plasticization. For example, U.S. Pat. No. 3,982,543 by Schmitt et al., issued Sep. 28, 1976, discusses lactic acid/glycolic acid copolymers and notes that solvents such as chloroform, xylene, and toluene soften the copolymer to obtain more sponge-like, woven, braided or felted surgical elements. Such solvents, however, are volatile compounds that aid processing, but that are not necessarily present as plasticizers in the final product.
Other processing aids even if not completely removed prior to formation of the final product, are not present in the product in a plasticizing role. U.S. Pat. No. 4,915,893 by Gogolewski et al., issued Apr. 10, 1990, discusses the use of additives to aid processing in the manufacture of biodegradable filaments, such as lactide/glycolide copolymer filaments. The additives allow the polymer to be more highly fibrillated during spinning than would be possible without the additives. The preferred additive is reported to be polyurethane which appears to be intended as a lubricant that aids spinning, but that is not completely removed from the final product. Other additives, such as glycolide, lactide, camphor, benzoic acid-2-hydroxyacetate, hexamethylbenzene, and 1,2-cyclohexanedione, however, are also discussed which do appear to be completely removed prior to finalizing the product under processing conditions disclosed therein. One example showing camphor as an additive discloses process conditions that would remove the additive during processing such that no additive was present in the final product. Also, many of the components, such as those disclosed by Schmitt et al. and Gogolewski et al., would present toxicity problems if present in a final degradable polymer composition.
The need for effective plasticized hydrolytically degradable compositions for mass-marketed products has not been adequately addressed in the prior art. The medical industry has focused on narrow applications, preferring to develop specific unplasticized copolymer compositions, and has not addressed the particular problems confronting mass-marketed products. A need exists for degradable polymer compositions that are suitable for use with mass-marketed products that can replace existing non-degradable products that are rapidly becoming difficult to dispose of due to limited landfill space and other environmental concerns.